Reaction with aryl hydroxylamines

Aryl hydroxylamines treated with acids rearrange to aminophenols. Although this reaction (known as the Bamberger rearrangement) is similar in appearance to... 

Aryl hydroxylamines treated with acids rearrange to aminophenols.255 Although this reaction (known as the Bamberger rearrangement) is similar in appearance to 1-32 to 1-36, the attack on the ring is not electrophilic but nucleophilic. The rearrangement is intermolecular, with the following mechanism ... 

Pyrroloindoles/ A simple route to this system, which is present as the corresponding quinone in mitomycins, can be obtained by reaction of N-aryl-hydroxylamines (1) with ethyl 6-oxo-2-hexynoate (2) to form a nitrone that is reduced without isolation with NaBHsCN (1.2 equiv.). 

A novel phenol-benzene coupling reaction,giving rise to 2- and 4-hydroxy-biphenyls, (249) and (250), occurs in the acid-catalysed reaction of JV-aryl-hydroxylamines (251) with benzene (Scheme 37). 

Diphenyl- -triazole is aminated by reaction with hydroxylamine-0-sulfonic acid. The I - and 2-aminotriazoles are formed in approximately equal amounts. Intramolecular amination of 1- and 2-aryltriazoles is achieved by generating a nitrene intermediate in the ortho position of the aryl substituent for example, in the thermolysis (Scheme 42) of the azide (17). ... 

The general approach to 0-arylation of hydroxylamines involves N-protection followed by O-arylation. Activated aryl halides and heteroaryl halides easily alkylate oxime salts (equation 25), N-aUcyl hydroxamic acids and N-hydroxysuccinimide . N-Hydroxyph-thalimide can be also 0-phenylated through a reaction with diphenyliodonium salt, although in lower yield . ... 

Acyl substituents at the 3- and/or 4-positions result in decreased hydrolytic stability compared with the alkyl and aryl derivatives described above. Despite this constraint most of the usual reactions of the carbonyl group are possible. Aldehydes <9ILA1211> and ketones are oxidized to the carboxylic acid, borohydride reduction affords the expected alcohols, and epoxides are formed on reaction with diazomethane. Oximes and arylhydrazones are formed with hydroxylamine and arylhydrazines, and the products may subsequently undergo monocyclic rearrangement involving the oxadiazole to give the corresponding isomeric furazans and 1,2,3-triazoles (Section 4.05.5.1.4). 

Although 3-aminoquinazoline derivatives are normally prepared de novo from hydrazine starting materials, they can also be prepared by N-amination reactions. Thus, treatment of l-substituted-2,4(177,377)-quinazolinediones 32 with 0-aryl hydroxylamines under basic conditions gives 3-amino-l-substituted-2,4(177,377)-quinazolinediones 33 which are intermediates in the synthesis of 3-amino-2,4(l/7,3/7)-quinazolinedione antibacterial agents <20020PD230, 2005JHC669, 2006JME6435>. 

Benzophenone imine is commercially available and serves as an ammonia surrogate that reacts with aryl halides in high yields under standard palladium-catalyzed conditions. Catalysts based on both DPPF- and BINAP-ligated palladium give essentially quantitative yields in reactions with aryl bromides (Eq. (23)). These reactions can be conducted with either CS2CO3 or NaOtBu as the base [179, 180]. The products are readily isolated by chromatographic techniques or by crystallization. Alternatively, they can be cleaved to the parent aniline by addition of hydroxylamine, acid, or Pd/C [180]. 

Because of their reactivity, aryl hydroxylamines can sometimes be trapped by further reaction with another material present in the hydrogenation system. Aryl nitrones such as 17 are produced by the in situ condensation of the aryl hydroxylamine with an aldehyde which is present in the reaction medium (Eqn. 19.16).35 These reactions take place in good yield over a Urushibara nickel catalyst (Chapter 12) in aqueous alcohol at room temperature and four... 

Bis(silyl)ketene acetals undergo silatropic ene reaction with nitrosobenzene to give N-hydroxyamino acid derivatives. When allylmagnesium chloride is reacted with nitroarenes, unstable adducts result. Reduction of these adducts with LAH in the presence of palladium on charcoal leads to A -allyl-W -aryl-hydroxylamines (73 Scheme 15). With alkyl Grignard reagents this reaction is negligible. ... 

An aryl cyclopropyl ketone reacted with hydroxylamine followed by a mixture of tosyl chloride and pyridine to give the corresponding 7V-arylcyclopropanecarboxamide as the sole product in fair yield.Alkyl cyclopropyl ketones, on the other hand, afforded mixtures of the corresponding A-alkylcyclopropanecarboxamide and A7-cyclopropylalkanamide in excellent total yield on reaction with hydrazoic acid (Schmidt reaction) in the presence of sulfuric acid or trichloroacetic acid, an example is the formation of 3. When sulfuric acid was used, the amide ratio was sensitive to the acid strength of the reaction mixture. ... 

Condensation reactions can be grouped into two categories. The first category involves pyrazol-3-ones with formyl, acyl, nitroso, a,jS-unsaturated oxo, 3-oxo-2-azobutyric acid ethyl ester or acetonitrile substituents at position 4 or formyl substituents at position 5 and their reaction with carbanions, heterocyclic methylcarbenium salts, primary and secondary amines, diamines, heterocyclic perchlorates, hydroxylamine, hydrazines, urea or thiosemicarbazide. The second category involves pyrazol-3-ones with amino, hydrazino, heteroaromatic amino, acetyl or acetonitiilo groups at position 4 and their reaction with aryl or heteroaromatic aldehydes or cyclic ketones. 

A route in which a synthon for such a dialdehyde is central depends on ortho lithiation of an aryl bromide for conversion to ortho bromoaryl aldehyde, then palladium-catalysed replacement of the halide with an alkyne, subsequent reaction with ammonia producing the isoquinoline. The sequence below shows how this type of approach can be used to produce naphthyridine mono-A-oxides by reaction of the alkynyl-aldehyde with hydroxylamine instead of ammonia. 

---